Foresight Update 27

Page 3

Recent
Progress: Steps Toward Nanotechnology

by Jeffrey Soreff

Advances in Proximal Probe Techniques

Proximal probes, primarily scanning tunneling microscopes
(STMs) and atomic force microscopes (AFMs) are important tools in
the development of nanotechnology. They permit an experimenter to
probe or modify a precisely chosen location. The following three
papers describe recent advances in these techniques.

Writing in [Science272: 1158-1161 24May96], P.E.
Sheehan and C.M. Lieber describe fabrication of a working
mechanical lock with a 58 nm wide crystal of MoO3 as
one of its moving parts. The authors grew several MoO3
crystals on a MoS2 substrate. They imaged, moved, and
machined the crystals with an AFM tip. Each of the crystals has a
preferred sliding direction along one of three
crystallographically equivalent directions parallel to the
surface of the hexagonal MoS2 substrate. The
orientation of a particular MoO3 crystal determines
which of the three directions is the preferred sliding direction
for this particular crystal. The MoS2 substrate
effectively locks the MoO3 crystals on to rails of
sulfur surface atoms. The locking is so strong that attempts to
push the crystals against their sliding directions cut them
instead. The ability to cut the crystals was used to cut one into
a latch for a second one. The atomic alignment with the substrate
(which sets the sliding directions) was an integral part of the
operation of this device. The authors write: "By sliding the
latch into the notch of crystal 2 (Fig. 4e), we effectively
locked the two nanocrystals, because crystal 2 could no longer
move along its preferred sliding direction of the MoS2
substrate. Hence, we created a nanometer-scale mechanical lock.
... More generally, we believe that our results represent an
important step toward the creation of nanometer-scale devices,
because they demonstrate the ability to machine complex shapes
and to reversibly assemble these pieces into interlocking
structures."

L.A. Bumm et. al., writing in [Science271:
1705-1707 22Mar96] describe evidence that single conjugated
molecules (4,4'-di(phenylene-ethnylene)benzenethiolate) can act
as single molecular wires. Electrical wires will be important in
many types of subsystems in nanotechnology. There are
instabilities that tend to destroy conductivity in
one-dimensional systems, so it is important to have experimental
bounds on how large these effects are. In this paper, a low
concentration of the conjugated molecules was embedded in a
self-assembled monolayer of n-dodecanethiol, a much less
conductive material. The composite monolayer (on an Au{111}
surface) was "probed by scanning tunneling microscopy (STM)
and microwave frequency alternating current STM at high junction
impedance (100 gigaohms)." The conjugated molecules could be
seem extending about 0.7 nm above the rest of the monolayer.
There are several lines of evidence that imply that the molecules
are isolated. In looking at images of several of these molecules,
they appear "with exactly the same shape, size, and
orientation, which is indicative of features that are much
sharper than the STM tip." Clusters of conjugated molecules
only appear at Au step edges, where the monolayer is expected to
be distorted. The isolated conjugated molecules are mostly found
at monolayer structural boundaries, but only at a small fraction
of these boundaries, "which indicates that their insertion
into the film is an isolated and improbable event." Finally,
the molecules are expected to be isolated because they are not
associated in the solution phase. Now that this work shows that
isolated conjugated molecules can successfully conduct current
through a monolayer, possible extensions might include attempting
localized electrochemical fabrication, or coupling an
electrically sensitive protein to the wire and changing its
conformation.

A longstanding problem in proximal probe work has been the
difficulty in determining the detailed geometry of the probe tip,
so that this may be accounted for in analyzing information from
the probe or in constructing structures with the probe. K.F.
Kelly et. al., writing in [J.Vac.Sci.Tech.B14: 593-596], describe imaging fullerene covered STM
tips. The authors' method uses in-situ reverse imaging of the tip
(as proposed by Drexler for AFM). In this paper, the sharp
objects used to create the image of the STM tip are defects in a
graphite substrate produced by argon ion bombardment. While the
defects are produced in a vacuum of 10-9 Torr, they
were able to use them in air. "Even though these defects are
larger than a few angstroms, their apices are narrow enough to
enable them to resolve the features of the tip-adsorbed fullerene
molecules." The authors propose mounting samples on the
ion-bombarded graphite so that a tip can be used for scanning the
samples and itself be evaluated by the defects on the portion of
the graphite that is not covered by the sample during the same
experiment. In the fullerene experiments, the role of the apical
atoms on the tips was played by several fullerene molecules
adsorbed on the tip. The authors found that "typically, when
a single or predominant fullerene molecule is imaged on the tip,
clear atomic resolution [by the tip] on graphite is observed. The
presence of several fullerene molecules of equivalent height
usually corresponds to little or no resolution of the underlying
graphite lattice." The authors explain that their technique
for imaging tips is preferable to several prior techniques. It is
preferable to some prior STM technique work, which had resolution
limited to tens of nanometers and had no way to identify the
actual tunneling region. It is preferable to field ion microscopy
because it is not limited to ultrahigh vacuum, and it allows
imaging during tunneling conditions rather than field evaporation
conditions.

Towards Machine Phase Synthesis

The following two papers describe some experiments in
solid-state chemistry which have some features in common with the
machine-phase synthetic processes. They show the potential speed
and specificity of reactions between rigidly held groups.

"...suggests
the utility of mechanochemistry at tool tips."

J.J. Gilman, writing in [Science274: 65
4Oct96], describes an analysis of mechanochemistry, albeit
focussing on reactions in sheared crystals rather than at the
tool tips of molecular machinery. Gilman emphasizes the
importance of the lower symmetry of a sheared system, as opposed
to a compressed one. In the case of sheared solids, he writes:
"Thus, the minimum (indirect) gap is decreased by shear but
is nearly unchanged by isotropic compression." One way to
view mechanochemistry at a tool tip is as a very high spatial
frequency, low symmetry, strain field. If we view tip chemistry
in this way, the enhanced efficacy of shear over compression in
producing reactions suggests the utility of mechanochemistry at
tool tips. Ideally, one would like to use something like x-ray
diffraction of sheared crystals of model compounds to confirm
predicted intermediate states in tool tip chemistry. Gilman
points out that the detonation of solid explosives is driven
mechanochemically, not thermally. This provides an experimental
proof of concept for high speed mechanochemical operations.

A different use of the rigidity of the solid state in chemical
reactions is described in [C&EN p34 19Aug96]. This
article describes a UV-induced carbene rearrangement of a diazo
compound which produces 4 isomers when carried out in solution,
but produces a single isomer in 96% yield when performed in the
solid state. According to the article, "Garcia-Garibay [an
assistant professor at UCLA] says that this [the high yield of
one isomer] is made possible by the order, homogeneity, and
rigidity of the crystal lattice housing the reaction." These
conditions are analogous to those expected for machine phase
synthetic processes.

Protein Design and Synthesis

Our best way for generating functional, extended, atomically
precise, nonperiodic, 3D structures is currently probably protein
synthesis. Our ability to exploit this technique is by limited
our ability to predict the folding of proteins into their stable
conformations and by the set of amino acids that we have
available for use in these proteins. The following four papers
describe advances in our ability to synthesize, design, and
exploit proteins.

"...broadens
the accessibility of unnatural amino acid residues"

M.J. O'Donnell, C. Zhou, and W.L. Scott, writing in [JACS118: 6070-6071 1996], describe a new method for adding
unnatural amino acid residues to peptides. The basic idea is to
add a glycine residue using standard peptide chemistry, activate
the terminal amine on the glycine by converting the amine into a
Schiff base with benzophenone, introduce the unnatural side chain
by alkylating the alpha-carbon of the glycine residue, then
hydrolyze off the benzophenone, leaving the unnatural amino acid
residue bound to the growing peptide. The main advantage of this
method is that it adds the special side chain in an alkylation
step, which can use a wide variety of alkyl halides. Previous
methods had required the separate synthesis of an amino acid
before adding it to the peptide. The advantage of this technique
to nanotechnologists is that it broadens the accessibility of
unnatural amino acid residues, which can assist in building more
rigid peptides with more predictable folding. The disadvantage of
the technique as it currently stands is that the alkylation isn't
stereospecific, so only 50% of each unnatural residue has a
particular orientation. Fortunately, the authors "are
currently exploring ... incorporation of
alpha,alpha-disubstituted residues, and stereoselective UPS
[unnatural peptide synthesis]."

M.D. Struthers, R.P. Cheng, and B. Imperiali, writing in [Science271: 342-345 19Jan96], describe the design of a 23-residue
peptide which folds into a stable tertiary structure. It does
this without assistance from complexed metal ions or disulfide
bridges. This work provides an example of a minimalist rigid
peptide structure. In order to build functional structures with
well defined geometries from flexible polymers such as peptides,
much of the design freedom in selecting the polymer must be used
to ensure that it folds into the desired structure. Sufficiently
small peptides have so few intramolecular interactions that they
can't fold stably at all. The invention of small, stably folding
peptides provides structural motifs that can guide the design of
functional structures. The smaller and stabler these motifs are,
the better they will assist in economizing on how much of the
design of a protein much be reserved to ensure its proper
folding. The authors' peptide consists of a beta hairpin turn and
an alpha helix. The design of the peptide went through five
iterations, starting with a sequence extracted from a natural
protein. Modifications were introduced to increase the stability
of the turn, originally dependent on Zn2+
coordination, but eventually stabilized with a D-proline in the
sequence. There is also a second unnatural amino acid, a
1,10-phenanthroline derivative, in the sequence. This is present
as a reporter group rather than to drive structure formation in
the final peptide. The authors confirmed the 3D structure of the
final peptide with NMR.

Writing in [Science274: 34-35 4Oct96], R.F.
Service describes some recent work towards improving the
understanding of beta sheet folding in proteins. Both alpha
helices and beta sheets are important structural elements in
proteins, but the formation of alpha helices is currently easier
to predict. The article describes a model compound built by
Norwick and coworkers that holds a "beta strand mimic--a
rigid, rodlike chemical group that forms hydrogen bonds with its
flexible peptide neighbor" together with two peptide
strands. The whole assembly forces all three strands into a beta
sheet when the proper amino acids are used in the peptide
strands. The group is using combinatorial chemistry to build
thousands of variations on this structure. Norwich says
"this allows us to juxtapose different amino acids next to
one another to see how it affects the structure and
stability" of the beta sheet folding.

S. Ueyama et. al. at Mitsubishi have built a molecular diode from
a modified cytochrome c552 protein [Inside R&D25:
1-2 6Mar96]. They bound flavin to the cytochrome, and were able
to demonstrate rectification with individual molecules imaged
between an STM tip and a gold substrate. The current flow goes
through both the flavin group and the heme group in the
cytochrome. The amino acids in the cytochrome are important in
preventing a direct connection between these two groups, thus
blocking reverse current flow when the voltage is reversed. This
development is helpful because the individual molecule used as a
diode contains many amino acid residues, each of which permits a
degree of design freedom in tuning the device for improved
performance.

DNA Technology

While proteins currently provide a way to combine 3D structure
with inclusion of functional groups, DNA has also been used to
construct complex 3D structures. The papers below describe two
groups' work in organizing nanoscale particles with DNA.

Two groups have recently described controlled assembly of Au
colloidal particles using DNA linkers. The two groups did their
experiments in rather different size regimes. C.A. Mirkin et. al,
writing in [Nature382: 607-609 15Aug96],
constructed their structures from 13-nm particles, while A.P.
Alivisatos et. al., writing in [Nature382: 609-611
15Aug96] used 1.4-nm clusters.

Mirkin's group attached two different, noncomplementary DNA
octomers to two batches of Au colloid. The octomers were attached
to the particles with thiol groups. The two sets of DNA-bound
colloidal particles were mixed, then a linking DNA strand,
complementary to one type of particle on one end and to the other
type on the other end, was added. This linked the particles
together into a mass which then precipitated. Mirkin's group
showed that this linkage is a noncovalent, reversible one. They
repeatedly cycled the material between an unlinked state and a
linked one by cycling the temperature above and below the
dissociation temperature (42C) of the DNA links. In contrast,
"Naked Au colloids do not aggregate in this manner under
comparable conditions, but rather undergo [irreversible]
particle-growth reaction." The aggregation is controlled by
the DNA pairing, which is highly specific. "In a control
experiment designed to verify that this process was due to
oligonucleotide hybridization, a duplex with four base-pair
mismatches in each of the 'sticky' ends of the linkers (step 2 in
Fig. 1) did not induce the reversible particle aggregation
process."

Alivisatos's group, on the other hand, bound a single
oligonucleotide strand to each of their clusters. Their
structures look more like DNA decorated with Au clusters, where
Mirkin's look more like Au clusters covered with DNA.
Alivisatos's group built several structures from their DNA-Au
cluster conjugates. They constructed several types of unlabelled
DNA strands which were complementary to various combinations of
Au-bound strands. They built two structures containing two Au
clusters in each structure. One of these brought the two clusters
together towards the center of the complementary strand, in a
"head-to-head" configuration. The other placed one of
the clusters towards the center of the complementary strand,
while the other was towards the end of the strand. A third
structure linked three DNA-linked Au clusters together.

Both groups examined their structures with electron microscopes.
Mirkin's group saw particle spacing of around 6nm, while
Alivisatos's saw spacings from 2-10 nm, depending on the
structure and on the conformation of the structure. One of the
comments in Mirkin's article is that "An advantage of the
DNA/colloid hybrid materials reported herein is that the
assemblies can be characterized easily by transmission electron
microscopy (TEM) and/or atomic force microscopy (AFM) as well as
spectroscopic methods conventionally used with DNA" in
contrast to the more difficult task of proving that a purely DNA
structure truly has the intended shape. Both groups expect to
extend this technique to other types of colloidal particles. As
in Seeman's
DNA polyhedra, the specificity of DNA pairing should allow
construction of complex geometries using this technique. The
addition of colloidal particles can potentially add structural
elements which are more rigid than any polymer strand to the set
of building blocks for nanometer-scale structures. To take full
advantage of this will require particles which are atomically
precise and which have several chemically distinct anchoring
points on each particle.

Fullerenes

The 1996 Nobel Prize in Chemistry was awarded to R.F. Curl,
H.W. Kroto, and R.E. Smalley for their discovery of fullerenes in
1985 (see this issue's
lead story and also nanotechnology news
story). From the perspective of nanotechnology, fullerenes
are potentially useful as stiff building blocks for larger
structures. The discovery of fullerenes has led to a wide variety
of work on their derivatives and on similar materials. One
related material that has attracted attention is
"nanotubes". Nanotubes are extended tubes of carbon
with radii of roughly 0.7nm. Smalley's lab has recently
discovered a method for efficiently
producing single-wall nanotubes [C&EN74:
5-6 29Jul96]. They have also "found a way to use a single nanotube as the tip of
an atomic force microscope." If the atomic configuration
at the tip is as well-controlled as it is in C60
itself, this would permit precise control of tips for both
probing and fabricating molecular structures with the microscope.
More generally, the nanotubes are stiff, and have small lateral
dimensions, both desirable properties for components for
nanoscale machinery.

Another recently discovered material related to the fullerenes is
a bowl-shaped molecule, C36H12, discovered
by L.T.Scott, M.S.Bratcher, and S. Hagen [C&EN74:
8-9 16Sep96]. It consists of a 36 carbon fragment of the 60
carbon fullerene structure, with the dangling bonds terminated
with hydrogen atoms. Unlike the fullerenes, which are prepared by
vaporizing carbon under special conditions, these experimenters
prepared their compound from a well-defined precursor
(decacyclene, C36H18). All but three of the
bonds present in the final compound are already present in the
precursor. It seems reasonable that a variety of related
structures (borazine-like ones, for instance, with BN pairs
substituted for adjacent carbon atoms) might be synthesized via
this route. This spectrum of rigid, carbon-rich, well-defined
structures could be useful as building blocks for nanostructures.

Software

In [C&EN74: 30-37 16Sep96] J.H. Krieger
covers a large number of developments in chemical software. A
good deal of the article covered WWW and user interface issues,
but there were some descriptions of advances in underlying
capabilities as well. Tripos introduced a technology called
"ChemSpace",
which allows searches for compounds with various characteristics
which are synthetically accessible. According to the article:
"because of the way ChemSpace designs a database, it won't
be generating compounds with interesting structures but which are
synthetically inaccessible. Because the reaction that builds any
compound is known and the reagents are known, it is possible for
a company to make the compound using that reaction and those
reagents." Since one of the major criticisms of theoretical
work in nanotechnology has been that we do not have the synthetic
capability to enable experimental tests of the theoretical
predictions in the near future, ChemSpace may be helpful in
discovering accessible structures which permit some of these
experimental tests.

Jeffrey Soreff is a researcher at IBM with an interest in
nanotechnology.